Quantitative analysis of cell-kill effects of anticancer drugs: consideration of both in vitro and in vivo experimental systems
Abstract
After examining the in vitro cell-kill kinetics of various anticancer drugs by using cultured human cell lines, Shimoyama et al. classified the drugs into two groups according to the types of action: 1) type-I drugs (cytocidal and concentration-dependent action) such as alkylating agents and anticancer antibiotics; 2) type-II drugs (cytostatic and time-dependent action) such as antimetabolites, Vinca alkaloids and L-asparaginase. In the present paper, we will present a rational basis for such a classification by using cell-kill pharmacodynamic models, and consider the optimal dosage regimen depending on the type of drugs by combining the cell-kill kinetic and pharmacokinetic models. In these models, classification of the drugs depends on whether the cell population is kinetically homogenous or not. It is assumed that cell population is homogenous for type-I drugs and there exist both drug sensitive and insensitive cell populations for type-II drugs. The concentration (or dose)-time-cell survival curves in both in vitro and in vivo, which are simulated based on the kinetic models, are consistent with the experimental data found in the literature. Further analysis on the optimal dose regimen according to these kinetic models clarified that the type-I drugs showed a similar cell-kill effect irrespective of the mode of administration as long as the area under the plasma unbound concentration curves (AUCp, free) is kept constant, while the type-II drugs are more effective by…
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Evidence Hub reads this as a review, done in animal and cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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